摘要:

Abstract:In this study we characterized the haplotypes found in IDDM patients that normally confer resistance to the disease in order to localize the polymorphisms relevant for the protection. We studied 15 DR2‐positive subjects with IDDM for their DRB1, DRB5 and DQB1 genes using RFLP, polymerase chain reaction (PCR), oligonucleotide typing, and in some specific cases direct sequencing after allele‐specific PCR. In addition we analyzed 39 DR2‐positive, IDDM non‐associated haplotypes representing those haplotypes that are not inherited to probands and hence are present only in healthy family members. The frequency of the DRB1*1501‐DRB5*0101‐DQB1*0602 haplotype was slightly decreased among diabetic patients (80% vs. 92%). In addition, two unconventional haplotypes DRB1*1501‐DRB5*0101‐DQB1*05031 and DRB1*1501‐DRB5*0101‐DQB1*0502 were found in patients with IDDM while all the control ones were conventional. The sequencing of the DQB1*0602 allele present in IDDM haplotypes showed no differences when compared to the controls. These results support the primary but not absolute role of DQ in the protection against IDDM. An additional role of factors centromeric to DQB1 gene was suggested by findings based on the biallelic TaqI RFLP polymorphism of the DQA2 gene. All DR2‐DQB1*0602 IDDM haplotypes were associated with the 2.1‐kb fragment while in the control group the 2.1‐kb and 1.9‐kb fragme

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02289.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:Detection of HLA‐C antigens by complement mediated cytotoxicity using human alloantisera is often difficult. Between 20 to 40% of individuals in every race have undectectable HLA‐C locus antigens and 9 out of the 29 sequenced HLA‐C alleles so far published encode serologically undetected antigens. In addition, HLA‐C molecules are expressed at the cell surface at about 10% of the levels of HLA‐A and HLA‐B. Recently, amplification of DNA using sequence‐specific primers (PCR‐SSP) has proved a reliable and rapid method for typing HLA‐DR, HLA‐DQA and HLA‐DQB genes. PCR‐SSP takes two hours to perform and is therefore suitable for the genotyping of cadaveric donors. We have designed a set of primers which will positively identify the HLA‐C alleles corresponding to the serologically defined series HLA‐Cw1, Cw2, Cw3, Cw4, Cw5, Cw6, Cw7 and Cw8. The serologically undetectable alleles have also been detected in groups according to sequence homology. In addition, three new unsequenced variants have been identified. DNA samples from 56 International Histocompatibility Workshop reference cell lines and 103 control individuals have been typed by the HLA‐C PCR‐SSP technique. 4/56 cell line types and 11/103 normal control individuals types were discrepant with the reported serological types. All combinations of serologically detectable and most of the serologically blank HLA‐C antigens can be readily identified. DNA typing for HLA‐Cw by PCR‐SSP can take as little as 130 minutes from start

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02290.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:A major aim of HLA and disease association studies is to identify the causative HLA factor truly responsible for the association. This is usually difficult due to the pronounced linkage disequilibrium between most HLA determinants. The causative factor must show the strongest association compared to all other factors. Here we describe a simple analysis which can be used to identify which of two factors, say A and B, shows the strongest association. The basic data for the analysis are the entries of the two‐by‐four table giving the four phenotypic combinations of A and B in patients and controls, respectively. These data are analyzed in various two‐by‐two tables involving stratification of each of the two factors against the other. A stronger increase of factor A is established if A is significantly associated with the condition both in B‐positives and in B‐negatives, when this is not true for B in A‐positives and A‐negatives. Using simulation with control data, it is demonstrated how linkage disequilibrium may influence secondary associations. The analysis may also be used to investigate interaction between HLA factors, but linkage disequilibrium complicates the interpretation in such cases. The method is exemplified using various published data. Finally, some statistical recommendations are given. Thus, we advise that phenotype (marker) frequencies are generally used instead of gene (i.e. allele, or haplotype) frequencies. The importance of correcting p‐values, the levels of significance, and the power of Fisher's exact t

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02291.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:Molecular studies of HLA‐DRB, ‐DRA and ‐DQB1 genes in the variant DR2 haplotype, DR2LUM, were performed using the homozygous lymphoblastoid cell line, CTS. The results of HLA Class II gene RFLP and PCR analyses suggest that DR2LUM was created by a homologous recombination event between HLA‐DR1 and HLA‐DR15 haplotypes. Evidence for the presence of a recombinational “hotspot” in haplotypes possessing a DRB6 pseudogene is presented. The results of this study have important implications for detection of HLA‐DR2 alleles in DRB gene oligotyping strategies, and suggest that the CTS cell line will be a useful addition to cell panels for characterizi

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02292.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) genes: HLA‐DRB, ‐DQA, ‐DQB, ‐DPB in 24 Danish patients with systemic lupus erythematosus (SLE) and in 102 healthy Danes. A highly significant increase of the frequency of the DR3‐ and DRw6‐associated 7.00 kb DRBTaqI DNA fragment was found in SLE patients compared to normal controls (83.3% vs 35.5%; RR = 9.1, p<10‐4). The frequencies of the DQA1*0501‐associated 4.56 kb DQATaqI fragment and the DRB3*01/03‐associated 9.79 kbTaqI fragment were also found to be significantly increased in SLE patients (70.8% vs 29.7%; RR = 5.8, p<10‐2for the DQA fragment and 70.8% vs 36.1%; RR = 4.3, p<0.05 for the DRB3 fragment). Less extensive and insignificant increases of the frequencies of the DR3‐associated DQB and DPB fragments were observed. The frequencies of the DR2‐associated DRB, DQA, and DQB fragments were comparable to those f

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02293.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:HLA‐B67 is an uncommon antigen that has been defined by serological crossreactivity with the HLA‐B7 and HLA‐B16 (B38 and B39) antigens. It is found at highest frequency in certain Oriental populations and has been best defined in the Japanese. Nucleotide sequencing of cDNA encoding B67 reveals the B*6701 allele to be a subtype of B39 which differs from B*39011 by substitution at residues 67–71 of the α1helix. In the region of difference B*6701 is identical in sequence to B7, B22, B27 and related molecules that express the epitope recognized by the ME1 monoclonal antibody. That the HLA‐B67 molecule binds strongly to the ME1 antibody was demonstrated by immunoprecipitation and cell surface binding assays. Identical B*6701 nucleotide sequences were obtained for the B67 alleles isolated from 2 unrelated Japanese and 1 North American

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02294.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02295.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02296.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02297.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02298.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY